ethyl (E)-3-(5-chlorobenzofuran-2-yl)-3-phenylacrylate | 1221963-54-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl (E)-3-(5-chlorobenzofuran-2-yl)-3-phenylacrylate
• 英文别名: (Z)-ethyl 3-(5-chloro-2-benzofuranyl)-3-phenylacrylate；(E)-ethyl 3-(5-chloro-2-benzofuranyl)-3-phenylacrylate；ethyl (E)-3-(5-chloro-1-benzofuran-2-yl)-3-phenylprop-2-enoate
• CAS: 1221963-54-7
• 化学式: C₁₉H₁₅ClO₃
• 分子量: 326.779
• InChiKey: UKDUMPCZIQEQCP-FOWTUZBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  39.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl (Z)-3-(5-chlorobenzofuran-2-yl)-3-phenylacrylate 、 ethyl (E)-3-(5-chlorobenzofuran-2-yl)-3-phenylacrylate 、 (Z)-3-(5-chlorobenzofuran-2-yl)-3-phenylacrylic acid 以(E)-3-(5-chloro-2-benzofuranyl)-3-phenylacrylic acid was obtained as yellowish solid的产率得到(E)-3-(5-chlorobenzofuran-2-yl)-3-phenylacrylic acid
  参考文献：
  名称：

  Allosteric protein kinase modulators

  摘要：

  本发明提供了一种特定的小分子化合物，可以变构地调节AGC蛋白激酶和Aurora家族蛋白激酶的活性或调节它们之间的蛋白质相互作用，以及制备它们的方法、包含它们的制药组合物，以及它们用于制备治疗与AGC蛋白激酶或Aurora家族蛋白激酶异常活性相关的疾病的药物。

  公开号：

  US08912186B2
• 作为产物：
  描述：

  (5-氯-1-苯并呋喃-2-基)-苯基甲酮 、 ethyl (Z)-3-(5-chlorobenzofuran-2-yl)-3-phenylacrylate 以(E)-ethyl 3-(5-chloro-2-benzofuranyl)-3-phenylacrylate was obtained as yellowish oil的产率得到ethyl (E)-3-(5-chlorobenzofuran-2-yl)-3-phenylacrylate
  参考文献：
  名称：

  Allosteric protein kinase modulators

  摘要：

  本发明提供了一种特定的小分子化合物，可以变构地调节AGC蛋白激酶和Aurora家族蛋白激酶的活性或调节它们之间的蛋白质相互作用，以及制备它们的方法、包含它们的制药组合物，以及它们用于制备治疗与AGC蛋白激酶或Aurora家族蛋白激酶异常活性相关的疾病的药物。

  公开号：

  US08912186B2

文献信息

• ALLOSTERIC PROTEIN KINASE MODULATORS
  申请人：Engel Matthias

  公开号：US20120046307A1

  公开（公告）日：2012-02-23

  The invention provides specific small molecule compounds that allosterically regulate the activity or modulate protein-protein interactions of AGC protein kinases and the Aurora family of protein kinases, methods for their production, pharmaceutical compositions comprising same, and their use for preparing medicaments for the treatment and prevention of diseases related to abnormal activities of AGC protein kinases or of protein kinases of the Aurora family.

  该发明提供了特定的小分子化合物，可以对AGC蛋白激酶和Aurora蛋白激酶家族的活性进行变构调节或调节蛋白质-蛋白质相互作用，以及制备它们的方法，包括它们的制药组合物，以及它们用于制备治疗与AGC蛋白激酶或Aurora家族蛋白激酶异常活性相关的疾病的药物的用途。
• 3,5-Diphenylpent-2-enoic Acids as Allosteric Activators of the Protein Kinase PDK1: Structure−Activity Relationships and Thermodynamic Characterization of Binding as Paradigms for PIF-Binding Pocket-Targeting Compounds†PDB code of <b>2Z</b> with PDK1: 3HRF.
  作者：Adriana Stroba、Francis Schaeffer、Valerie Hindie、Laura Lopez-Garcia、Iris Adrian、Wolfgang Fröhner、Rolf W. Hartmann、Ricardo M. Biondi、Matthias Engel

  DOI：10.1021/jm9001499

  日期：2009.8.13

  The modulation of protein kinase activities by low molecular weight compounds is a major goal of current pharmaceutical developments. In this line, important efforts are directed to the development of drugs targeting the conserved ATP binding site. However, there is very little experience on targeting allosteric, regulatory sites, different from the ATP binding site, in protein kinases. Here we describe the synthesis, cell-free activation potency, and calorimetric binding analysis of 3,5-diphenylpent-2-enoic acids and derivatives as allosteric modulators of the phosphoinositide-dependent kinase-1 (PDK 1) catalytic activity. Our SAR results combined with thermodynamic binding analyses revealed both favorable binding enthalpy and entropy and confirmed the PIF-binding pocket of PDK I as a druggable site. In conclusion, we defined the minimal structural requirements for compounds to bind to the PIF-binding pocket and to act as allosteric modulators and identified two new lead structures (12Z and 13Z) with predominating binding enthalpy.